4. Conclusions
DNA damage can occur throughout life; therefore, it is fundamental for
DNA repair to occur to preserve the genetic material encoded. NER is one
of the repair pathways, and it is responsible for the removal and repair
of bulky lesions within the DNA. NER has two subpathways, GG-NER and
TC-NER, both of which play an important role and require the recruitment
and activity of the TFIIH complex. TFIIH is important for damage
verification, unwinding of the DNA, and holding open the excision bubble
for the other NER proteins to function. When defects occur in the
proteins in TFIIH and the proteins throughout the rest of the pathway,
genetic disorders will occur with varying clinical phenotypes and
severity. Proteins within the TFIIH complex also provide therapeutic
targets in cancer chemotherapeutic treatments to different cancers and
understanding mechanisms of resistance within them as well.
However, despite the extensive research and knowledge on the NER pathway
and the TFIIH complex, there are still many knowledge gaps regarding the
detailed functions of TFIIH in NER. For example, how do XPB and XPD
coordinate to open the two DNA strands? What exact roles does TFIIH play
in TC-NER? Why germline mutations in XPD, some of them occur in residues
close to each other (e.g., Arg601 and Gly602)(Lehmann, 2001), exhibit
significantly different clinical phenotypes? More research is needed to
further elucidate the mechanisms and the role of each of the individual
subunits of the TFIIH complex in both transcription and the NER pathway.